초록
<P><B>Abstract</B></P><P>Chemical and biocatalytic synthesis of non‐canonical α‐amino acids (ncAAs) from renewable feedstocks and using mild reaction conditions has not efficiently been solved. Here, we show the development of a three‐step, scalable and modular one‐pot biocascade for linear conversion of renewable fatty acids (FAs) into enantiopure <SMALL>l</SMALL>‐α‐amino acids. In module 1, selective α‐hydroxylation of FAs is catalyzed by the P450 peroxygenase P450<SUB>CLA</SUB>. By using an automated H<SUB>2</SUB>O<SUB>2</SUB> supplementation system, efficient conversion (46 to >99%; TTN>3300) of a broad range of FAs (C6:0 to C16:0) into valuable α‐hydroxy acids (α‐HAs; >90% α‐selective) is shown on preparative scale (up to 2.3 g L<SUP>−1</SUP> isolated product). In module 2, a redox‐neutral hydrogen borrowing cascade (alcohol dehydrogenase/amino acid dehydrogenase) allowed further conversion of α‐HAs into <SMALL>l</SMALL>‐α‐AAs (20 to 99%). Enantiopure <SMALL>l</SMALL>‐α‐AAs (e.e. >99%) including the pharma synthon <SMALL>l</SMALL>‐homo‐phenylalanine can be obtained at product titers of up to 2.5 g L<SUP>−1</SUP>. Based on renewables and excellent atom economy, this biocascade is among the shortest and greenest synthetic routes to structurally diverse and industrially relevant ncAAs.</P>